Recent progress in the development of alcoholic typologies and the identification of salient patient characteristics has resulted in renewed interest in patient-treatment matching. Rigorous efforts to match patient characteristics with specific treatments, while yielding promising results, have been limited largely to psychotherapies. However, developments in clinical neurobiology are rapidly being applied to the study of the pathophysiology of alcoholism. Consequently, there is renewed interest in the pharmacotherapy of alcohol dependence and a number of trials of promising medications are currently underway in alcoholics. The specific aims of this proposal are: 1) To evaluate the efficacy of fluoxetine, a selective serotonergic antidepressant, as an adjunct to coping skills training in a sample of outpatient alcoholics, based on a study that is underway at the UConn ARC. 2) To evaluate the utility of matching subtypes of alcoholics to treatment with fluoxetine 3) To examine the concurrent validity of recently developed typologies of alcoholism, through pharmacologic challenges with m-CPP/ritanserin and yohimbine/clonidine, aimed at specific monoamine neurotransmitters (serotonergic and alpha-2-adrenergic systems, respectively) that are relevant to alcoholism. 4) To generate matching hypotheses, based on the results of Aims 2 and 3 above, that can be prospectively tested in a clinical trial of a promising, but as yet undetermined, medication for the treatment of alcoholism. Efforts to achieve these aims will provide the basis for the development of the candidate, Henry Kranzler, M.D. as a clinical investigator in alcoholism. Three nationally-prominent clinical investigators will serve as preceptors for Dr. Kranzler and the highly-trained personnel and resources of two federally-funded alcohol research centers will be accessible to him in this effort.